Psychosis associated with leukodystrophies

Facts box Inherited leukodystrophies are under recognized and under diagnosed in psychiatric populations. Psychiatric illness in patients with leukodystrophies may be indistinguishable from primary psychiatric disorders. Individuals with later-onset forms of inherited metabolic disorders are more likely to develop - and may present solely with - psychiatric illness. The diagnosis of an inherited leukodystrophy should be considered in patients with psychiatric illness and concurrent seizures or cognitive decline. Individuals with psychiatric illness and an underlying inherited metabolic disorder are often treatment resistant. Failure to diagnose an inherited metabolic disorder can impede treatment and have fatal consequences for certain patients. Use of psychotropic medications in patients with inherited metabolic disorders has the potential to worsen the underlying disease process and produce serious side effects. Introduction The term leukodystrophy refers to diseases of the white matter, which results in a functional “disconnection” between parts of the nervous system that communicate through the affected white-matter tracts. The clinical consequences of this “disconnection” depend on the localization of the white-matter pathology, whether it is in the brain, spinal cord, or brain stem. What are the principal clinical consequences of lesions that interrupt the white-matter bundles involved in cortico-cortical interactions? In this case, one might expect the result to be a disturbance of mental function. In other words, a leukodystrophy that targets the white matter of the brain will tend to produce psychiatric symptomatology.In this chapter, we review the major inherited leukodystrophies, with attention to the psychiatric manifestations associated with each.